Malignant gliomas are rapidly growing primary brain tumors associated with a high degree of morbidity and mortality. Current management is based on cytoreduction through a combination of surgery, radiotherapy and chemotherapy. Despite this multidisciplinary approach to treatment, malignant glioma remains a life-threatening disease. This is a multicenter, randomized, open-label, Phase II reference agent trial designed to determine the efficacy and safety of temozolomide in the treatment of patients with GBM at first relapse. The reference agent is included to verify that objective responses for procarbazine, can be seen within the definition of the protocol in a contemporaneously randomized group of patients using state-of-the-art techniques, and to allow a contrast of the reference agent to the literature. The primary objectives are to determine the efficacy of temozolomide defined as progression-free survival at 6 months and safety of temozolomide when administered orally. The secondary objectives are: a) to describe the health-related quality of life of all patients enrolled on temozolomide and the reference agent, procarbazine b) to assess population-based pharmacokinetics in patients receiving temozolomide and c) to assess overall survival for all patients enrolled on temozolomide and the reference agent procarbazine. Enrollment has just begun.